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Armitage E.G.,University of San Pablo - CEU | Barbas C.,University of San Pablo - CEU
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

Cancer research is one of the largest fields in the life sciences and despite many astounding breakthroughs and contributions over the past few decades, there is still a considerable amount to unveil on the function of cancer. It is well known that cancer metabolism differs from that of normal tissue and an important hypothesis published in the 1950s by Otto Warburg proposed that cancer cells rely on anaerobic metabolism as the source for energy, even under physiological oxygen levels. Following this, cancer central carbon metabolism has been researched extensively and beyond respiration, cancer has been found to involve a wide range of metabolic processes, and many more are still to be unveiled. Studying cancer through metabolomics could reveal new biomarkers for cancer that could be useful for its future prognosis, diagnosis and therapy. Metabolomics is becoming an increasingly popular tool in the life sciences since it is a relatively fast and accurate technique that can be applied with either a particular focus or in a global manner to reveal new knowledge about biological systems. There have been many examples of its application to reveal potential biomarkers in different cancers that have employed a range of different analytical platforms. In this review, approaches in metabolomics that have been employed in cancer biomarker discovery are discussed and some of the most noteworthy research in the field is highlighted. © 2013 Elsevier B.V.

Dominguez G.,University of San Pablo - CEU | Perez-Castells J.,University of San Pablo - CEU
Chemical Society Reviews | Year: 2011

The [2+2+2] cycloaddition is an elegant, atom-efficient and group tolerant process for the synthesis of carbo- and heterocycles, mostly aromatic, involving the formation of several C-C bonds in a single step. Cyclotrimerisation is catalyzed by a variety of organometallic complexes, including more than 15 different metals. The aim of this tutorial review is to point out the most recent advances in this field and to encourage the use of this reaction enroute to complex molecules. After summarizing the most common catalysts and reaction conditions generally used, we survey the mechanistic features currently accepted for this reaction. Section 4 covers the scope of the different [2+2+2] cycloaddition versions starting with the cyclotrimerisation of three triple bonds, including nitriles, with especial emphasis on asymmetric reactions that create central, axial or planar chirality. Then, reactions that use double bonds are addressed. Finally, the most outstanding examples of natural products synthesis using [2+2+2] cycloadditions as a key step reported recently are shown. © 2011 The Royal Society of Chemistry.

Vidal-Vanaclocha F.,University of San Pablo - CEU
Cancer Microenvironment | Year: 2011

Colon cancer frequently metastasizes to the liver but the genetic and phenotypic properties of specific cancer cells able to implant and grow in this organ have not yet been established. The contribution of the patient's genetic, physiologic and pathologic backgrounds to the incidence and development of hepatic colon cancer metastases is also presently misunderstood. At a transcriptional level, hepatic metastasis development is in part associated with marked changes in gene expression of colon cancer cells that may originate in the primary tumor. Other changes occur in the liver and are regulated by hepatic cells, which represent the new microenvironment for metastatic colon cancer cells. However, hepatic parenchymal and non-parenchymal cell functions are also affected by both tumor-derived factors and systemic host factors, which suggests that the hepatic metastasis microenvironment is a functional linkage between the hepatic pathophysiology of the colon cancer patient and the biology of its cancer cells. Therefore, together with metastasis-related gene profiles suggesting the existence of liver metastasis potential in primary tumors, new biomarkers of the prometastatic microenvironment supported by the liver reaction to colon cancer factors may be helpful for the individual assessment of hepatic metastasis risk in colon cancer patients. In addition, knowledge on hepatic metastasis gene regulation by the hepatic microenvironment may open multiple opportunities for therapeutic intervention during colon cancer metastasis at both subclinical and advanced stages. © Springer Science+Business Media B.V. 2011.

Moxon K.A.,Drexel University | Foffani G.,University of San Pablo - CEU | Foffani G.,Hospital Nacional Of Paraplejicos
Neuron | Year: 2015

The field of invasive brain-machine interfaces (BMIs) is typically associated with neuroprosthetic applications aiming to recover loss of motor function. However, BMIs also represent a powerful tool to address fundamental questions in neuroscience. The observed subjects of BMI experiments can also be considered as indirect observers of their own neurophysiological activity, and the relationship between observed neurons and (artificial) behavior can be genuinely causal rather than indirectly correlative. These two characteristics defy the classical object-observer duality, making BMIs particularly appealing for investigating how information is encoded and decoded by neural circuits in real time, how this coding changes with physiological learning and plasticity, and how it is altered in pathological conditions. Within neuroengineering, BMI is like a tree that opens its branches into many traditional engineering fields, but also extends deep roots into basic neuroscience beyond neuroprosthetics. © 2015 Elsevier Inc.

Amphetamine treatment during adolescence causes long-term cognitive deficits in rats. Pleiotrophin (PTN) is a cytokine with important roles in the modulation of synaptic plasticity, whose levels of expression are significantly regulated by amphetamine administration. To test the possibility that the long-term consequences of periadolescent amphetamine treatment cross species and, furthermore, to test the hypothesis that PTN could be one of the factors involved in the adult cognitive deficits observed after periadolescent amphetamine administrations, we comparatively studied the long-term consequences of periadolescent amphetamine treatment (3 mg/kg intraperitoneal, daily during 10 days) in normal wild-type (PTN+/+) and in PTN genetically deficient (PTN-/-) mice. Within the first week after cessation of treatment, significant deficits in the passive avoidance and Y-maze tests were only observed in amphetamine-pretreated PTN-/- mice. However, 13 and 26 days after the last administration, we did not find significant differences in Y-maze between amphetamine- and saline-pretreated PTN-/- mice. In addition, we did not find any genotype- or treatment-related anxiogenic- or depressive-like behaviour in adult mice. Furthermore, we observed a significantly enhanced long-term potentiation (LTP) in CA1 hippocampal slices from saline-pretreated PTN-/- mice compared with saline-pretreated PTN+/+ mice. Interestingly, amphetamine pre-treatment during adolescence significantly enhanced LTP in adult PTN+/+ mice but did not cause any effect in PTN-/- mice, suggesting LTP mechanisms saturation in naïve PTN-/- mice. The data demonstrate that periadolescent amphetamine treatment causes transient cognitive deficits and long-term alterations of hippocampal LTP depending on the endogenous expression of PTN. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

Agency: European Commission | Branch: H2020 | Program: IA | Phase: ICT-20-2015 | Award Amount: 6.43M | Year: 2016

NEWTON is a large scale initiative to develop, integrate and disseminate innovative technology-enhanced learning (TEL) methods and tools, to create new or inter-connect existing state-of-the art teaching labs and to build a pan-European learning network platform that supports fast dissemination of learning content to a wide audience in a ubiquitous manner. NEWTON focuses on employing novel technologies in order to increase learner quality of experience, improve learning process and increase learning outcome. The NEWTON project goals are to: 1) develop and deploy a set of new TEL mechanisms involving multi-modal and multi-sensorial media distribution. 2) develop, integrate, deploy and disseminate state of the art technology-enhanced teaching methodologies including augmented reality, gamification and self-directed learning addressed to users from secondary and vocational schools, third level and further education, including students with physical disabilities, 3) build a large platform that links all stakeholders in education, enables content reuse, supports generation of new content, increases content exchange in diverse forms, develops and disseminates new teaching scenarios, and encourages new innovative businesses. 4) perform personalisation and adaptation for content, delivery and presentation in order to increase learner quality of experience and to improve learning process, and 5) validate the platform impact and the effectiveness of the teaching scenarios in terms of user satisfaction, improvement of the learning and teaching experience, etc. and the underlying technology through an European-wide real-life pilot with 4 different scenarios. The real-life validation will involve all major stakeholders in TEL area, from content providers, innovative idea creators, technology developers, regulators, associations, schools and teachers in a large-scale pilot covering 26 institutions (14 funded from the NEWTON project \ 12 a partners) in 7 European countries.

University of Valladolid and University of San Pablo - CEU | Date: 2011-02-02

The invention relates to novel fluorescent compounds analogous to alkyl phospholipids, containing highly photostable fluorescent groups in the structure thereof and emitting in the visible spectrum wavelength range. Said compounds are easily introduced into micro-organisms, enabling the detection and identification of said organisms by means of fluorescence microscopy. The novel fluorescent compounds can also diagnose, rapidly and easily, the presence of pathogenic micro-organisms characterised by their resistance to treatment with alkyl phospholipids.

Device for measuring the amount of flowing liquid, which device is composed of a liquid recipient (2) divided into two chambers (4, 5), an external valve (6), a flexible tube (7) and a calculation unit (10) and is characterized in that the liquid recipient (2) has two capacitive sensors (11, 12) installed in the external wall thereof, which sensors measure the liquid level in each chamber. The measurement method is characterized in that the volume of liquid V contained in the first chamber (4) of volume R is measured with an interval T using the first capacitive sensor (11), and, when V R , it is determined whether the liquid is allowed to pass to the second chamber (5), where the volume is measured using the second capacitive sensor (12), or the external valve (6) is opened and the measurement process is restarted.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.01M | Year: 2012

Coding of biochemical information is commonly described to be based solely on nucleotides and amino acids, whereas carbohydrates, the most abundant type of molecule in Nature, appear sidelined in this respect. That carbohydrates, as part of cellular glycoconjugates, have exceptional talents for building biochemical signals is an emerging insight, at the heart of the concept of the Sugar Code. Intuitively, emergence of recognition partners for information transfer is expected, and this is the case. Thus, coding of bioinformation in glycans and information transfer via lectins is key to a wealth of medically relevant processes, e.g. infection, immune regulation and malignancy, now awaiting its full exploitation pharmaceutically. To do so, training in this exceptionally interdisciplinary field needs to be provided. With this aim, scientific and country/gender issues are strategically combined in this network. Its composition assures a continuous chain of research expertise, from computational and synthetic chemistry to state of the art biophysical chemistry and structural biology, then to biochemistry, molecular cell biology and pharmaceutical/biomedical sciences, generating innovative clinical approaches. Notably, academia is linked with industry, bringing in the essence of business acumen into the training programme. This activity and the research deliberately planned as interdisciplinary projects ensure an optimal training for young researchers in a dynamically developing area of conspicuous biopharmaceutical potential. Equally important, it lays the foundation to inspire novel strategies for the design of potent and selective inhibitors against lectins and the development of lectins (or suitably engineered variant(s)) as therapeuticals. As a boon for the success of the network, cooperations between several partners have already proven successful, especially increasing the core in Madrid and partners in Dublin, Munich and Prague.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 3.04M | Year: 2010

The lung is probably one of the most difficult organs to study by MRI because of its low proton density. Still, MRI is very interesting as not exposure of ionizing radiation to patients and its important role for translatability studies. Moreover, assessment of regional pulmonary perfusion and ventilation with clinical value as an indicator of lung function by MRI has been demonstrated using MRI based techniques both with hyperpolarized and fluorinated gases, oxygen and contrast agent free methods. The -net ITN will undertake successful efforts (funded under the fifth and six framework program) and previous bilateral collaborative and complementary work of different European research teams to contribute to the field of lung functional MRI. -net proposes very complementary and strongly interlinked research and training activities for these functional studies. The main research activity line aims at applying MRI based techniques for diagnosis (human and preclinical activities) and treatment (only preclinical) monitoring of lung diseases (COPD, lung cancer, cystic fibrosis, asthma), without excluding the possibilities that other imaging techniques (nuclear, CT and optical imaging) and molecular approaches (including molecular imaging and metabolomic analysis) may bring to the field. -net plans a training program to provide new ESR high level multidisciplinary scientific education and complementary skills for animal studies, MRI and other imaging techniques, and on translational aspects of research. The network is formed by 9 groups, located in 5 different countries (Spain, France, UK, Germany and Sweden). The centres hold researchers with previous experience in the network work and with researchers with high quality scientific production rate, and with experience in MRI physics, therapy, clinical, physiopathological and molecular aspects of respiratory diseases.

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